Matrix metalloproteinase-9 in the pathophysiology and diagnosis of dry eye syndrome

Abstract

Dry eye and tear dysfunction are common ocular disorders that cause cornea barrier disruption resulting in a poorly lubricated and irregular cornea epithelium, eye irritation and blurred vision. Increased levels and activities of matrix metalloproteinases (MMPs), particularly MMP-9, have been detected in the tears and ocular surface epithelial and inflammatory cells in dry eye. MMPs have been found to participate in disruption of tight junctions in the apical cornea epithelium leading to their accelerated desquamation and barrier disruption. This review summarizes evidence showing the contribution of MMPs to dry eye pathogenesis and their roles as biomarkers and therapeutic targets. Keywords: matrix metalloproteinase, dry eye, keratitis sicca, cornea, barrier function, Sjögren syndrome Dry eye overviewDry eye and tear dysfunction are common ocular disorders that cause cornea barrier disruption resulting in a poorly lubricated and irregular cornea epithelium, eye irritation and blurred vision. It affects millions of people worldwide and is one of the most frequent conditions for which patients seek eye care.1 Aging and female sex are significant risk factors for dry eye which increases in prevalence around the fifth decade, with further increase every decade thereafter.2-13 Prevalence of dry eye varies from 2% to 50%, depending on the population studied and the diagnostic criteria for dry eye (symptom questionnaire vs. objective signs). [1][2][3]6,7,[9][10][11][14][15][16][17][18][19][20][21][22][23] There is scarce information about the natural history of dry eye, but there is a recognized disconnection between signs and symptoms; patients tend to be more symptomatic at early stages.24,25 Dry eye causes corneal irregularity [26][27][28] and decreases functional vision by altering contrast sensitivity [29][30][31] and, therefore, decreases quality of life with a significant burden on the individual as well as the society. 23,[32][33][34][35] A meta-analysis of 22 published studies showed increased odds ratio for depression and anxiety in patients with ocular Sjögren syndrome (SS). 36 There is increased evidence that dry eye is an inflammatory disease, and this review will focus on matrix metalloproteinases (MMPs) and their role in the pathogenesis of dry eye. Cornea barrier disruption is a feature of dry eyeAs the principal lens of the eye, the cornea has unique features to maintain its transparency and smooth surface that include a lack of blood vessels and a multilayered stratified, non-cornifying epithelium. The differentiated apical epithelial cells produce

The Protective Effect of Polygonum cuspidatum (PCE) Aqueous Extract in a Dry Eye Model

“…In the case of MMP9, this enzyme lyses the various components of the corneal epithelial basement membrane and tight junction proteins such as ZO-1 and occludin to maintain corneal epithelial barrier function [ 43 , 44 ]. Increased MMP9 activity in DED is related to a dysfunctional epithelial barrier, increased corneal epithelial erosions, and corneal surface irregularity [ 45 , 46 ] Our findings revealed that PCE inhibited the increase in MMP9 mRNA expression in DED.…”

Autophagy Activation Protects Ocular Surface from Inflammation in a Dry Eye Model In Vitro

“…Different from the inflammation factors activated at 4 h, autophagy is a late response to hyperosmotic stress in HCECs at 24 h. After autophagosome formation in HCECs exposed to hyperosmolarity, evidenced by the increases of Beclin1, Atg5, Atg7 and LC3B, as well as the decrease of P62, a few upward blips in cell viability were observed, accompanied by a moderate drawdown of TNF-α, IL-1β, IL-6 as well as IL-8. Autophagy modulates inflammation through influencing the inflammatory cells survival conditions and altering secretion of inflammatory cytokines [ 33 , 44 ], by which autophagy is simultaneously modulated [ 24 ]. Thus, we assessed how modulators of autophagy can relieve ocular surface inflammation linked with dry eye disease.…”

NSAID-induced corneal melt: Clinical importance, pathogenesis, and risk mitigation

“…MMPs participate in the disruption of tight junctions in the apical corneal epithelium leading to their accelerated desquamation and barrier disruption. 67 The role of MMPs in corneal melt, intuitive if one considers the predominance of collagen in the structure of corneal stroma, is well documented. 7,8,57,63,76,87 Specifically for NICM, the study of three cases of diclofenac-induced corneal melt with perforation revealed enhanced expression of MMPs 1 and 9 within corneal epithelial cells, stromal keratocytes, and at the level of the Descemet membrane.…”